6A1C
Crystal structure of the CK2a1-go289 complex
Summary for 6A1C
| Entry DOI | 10.2210/pdb6a1c/pdb |
| Descriptor | Casein kinase II subunit alpha, 5-bromanyl-2-methoxy-4-[(E)-(3-methylsulfanyl-5-phenyl-1,2,4-triazol-4-yl)iminomethyl]phenol, SODIUM ION, ... (5 entities in total) |
| Functional Keywords | ck2a1, inhibitor, complex, transferase |
| Biological source | Homo sapiens (Human) |
| Total number of polymer chains | 1 |
| Total formula weight | 42534.24 |
| Authors | Kinoshita, T.,Tsuyuguchi, M. (deposition date: 2018-06-07, release date: 2019-03-06, Last modification date: 2023-11-22) |
| Primary citation | Oshima, T.,Niwa, Y.,Kuwata, K.,Srivastava, A.,Hyoda, T.,Tsuchiya, Y.,Kumagai, M.,Tsuyuguchi, M.,Tamaru, T.,Sugiyama, A.,Ono, N.,Zolboot, N.,Aikawa, Y.,Oishi, S.,Nonami, A.,Arai, F.,Hagihara, S.,Yamaguchi, J.,Tama, F.,Kunisaki, Y.,Yagita, K.,Ikeda, M.,Kinoshita, T.,Kay, S.A.,Itami, K.,Hirota, T. Cell-based screen identifies a new potent and highly selective CK2 inhibitor for modulation of circadian rhythms and cancer cell growth. Sci Adv, 5:eaau9060-eaau9060, 2019 Cited by PubMed Abstract: Compounds targeting the circadian clock have been identified as potential treatments for clock-related diseases, including cancer. Our cell-based phenotypic screen revealed uncharacterized clock-modulating compounds. Through affinity-based target deconvolution, we identified GO289, which strongly lengthened circadian period, as a potent and selective inhibitor of CK2. Phosphoproteomics identified multiple phosphorylation sites inhibited by GO289 on clock proteins, including PER2 S693. Furthermore, GO289 exhibited cell type-dependent inhibition of cancer cell growth that correlated with cellular clock function. The x-ray crystal structure of the CK2α-GO289 complex revealed critical interactions between GO289 and CK2-specific residues and no direct interaction of GO289 with the hinge region that is highly conserved among kinases. The discovery of GO289 provides a direct link between the circadian clock and cancer regulation and reveals unique design principles underlying kinase selectivity. PubMed: 30746467DOI: 10.1126/sciadv.aau9060 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.68 Å) |
Structure validation
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